The effectiveness of adoptive cellular immunotherapy depends on the ability of the infused cells to survive in the recipient host and to implement a potent anti-tumor response. An ideal source of such lymphoid cells is the tumor-bearer's own cells since they are not only histocompatible but also primed to tumor antigens. Our goal is to generate maximal levels of anti-tumor cytotoxicity in tumor-bearer lymphoid cells and to evaluate the therapeutic value of such cells. To achieve this goal we will first identify; 1) The cellular requirements for the generation and expression of anti-tumor cytotoxicity in tumor-bearer spleen cells upon in vitro activation with stimulator tumor cells; 2) the nature of the suppressor cell(s) among tumor-bearer lymphoid cells as well as their mode of action in inhibiting the anti-tumor activity in tumor-bearer spleen cells that are cultured in the presence or absence of stimulator tumor cells. This information will guide us in the search for methods to selectively stimulate potentially cytotoxic cells and/or selectively remove suppressor cells resulting in the generation of augmented levels of anti-tumor cytotoxicity upon in vitro activation. We will evaluate the homing patterns of activated tumor-bearer lymphoid cells and determine whether changes in the tendency of infused cells to home to lymph nodes draining the site of tumor injection can be used to screen lymphoid cells for their potential effectiveness in transferring systemic anti-tumor activity. The effectiveness of infused activated tumor-bearer lymphoid cells in transferring systemic anti-tumor activity will be determined in relation to the tumor burden that they can cope with. We will employ adoptive immunotherapy as an adjunct to cytostatic therapy for specific eradication of residual tumor cells. We will evaluate the nature of immunity in mice cured of tumor following immunotherapy to determine which anti-tumor responses are altered and augmented in comparison with these responses in mice with progressively growing tumors.